Cells from individuals with SOD-1 associated familial amyotrophic lateral sclerosis do not have an increased susceptibility to radiation-induced free radical production or DNA damage.

Oxidative stress may play a role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS). Superoxide dismutases (SODs) are enzymes that can influence free radical processes in irradiated cells and there is some evidence that manipulation of SODs can affect survival of cells after radiation treatments. SOD-1 associated FALS mutants may have an altered radiation response due to an enhanced generation of hydroxyl radicals or a compromised ability to neutralize free radicals. We have investigated the ability of the lymphoblastoid cell lines from FALS patients with SOD-1 gene mutations, patients with sporadic ALS and controls to handle oxidative stress induced by ionising radiation by measuring levels of intracellular reactive oxygen species and production of DNA double-strand breaks. Levels of reactive oxygen species, expressed as the slope of the relative fluorescence of a radical-reactive fluorochrome, in the cells from familial ALS patients with SOD-1 gene mutations (2.14+/-1.06 Gy(-1)) and patients with sporadic ALS (1.38+/-0.21 Gy(-1)) were not significantly different from the controls (1.54+/-0.39 Gy(-1)). No significant difference was observed in the production of DNA double-strand breaks between three groups. The ability of lymphoblastoid cells from FALS patients with SOD-1 gene mutations to scavenge radiation-induced free radicals is not compromised nor is their ability to protect DNA damage induced by ionising radiation.

DNA strand break rejoining defect in xrs-6 is complemented by transfection with the human Ku80 gene.

The radiosensitive mutant xrs-6, derived from Chinese hamster ovary cell line CHO-K1, has been demonstrated to be defective in DNA double-strand break repair and also in its proficiency to undergo V(D)J recombination. Recent work has provided both genetic and biochemical evidence that the M(r) 80,000 subunit of the Ku protein is able to complement the radiosensitivity and the V(D)J recombination defect in the xrs-6 mutant. We demonstrate here that complementation of the radiosensitive phenotype in xrs-6 cells by the introduction of Ku80 cDNA is accompanied by the concomitant restoration of DNA double-strand break rejoining proficiency to almost that of the parental CHO-K1 cells, as measured both by neutral single-cell microgel electrophoresis (Comet) technique and by pulsed-field gel electrophoresis. These results provide further biochemical evidence for the involvement of the Ku protein in the repair of DNA double-strand breaks.

Radiotherapy for bone pain.

Painful bone metastases are a common problem for cancer patients. Although current evidence supports the use of a single fraction of radiotherapy as the treatment of choice, many radiotherapists, for a variety of reasons, continue to use fractionated regimens. Over one six month period 105 patients received external beam irradiation for painful bone metastases at the Royal London Hospital (RLH). Thirty-one per cent of the patients were aged 70 or over. The treatment of 97 of these patients was assessed. They had a total of 280 sites treated over the course of their disease. Fifty-nine per cent of sites treated received a fractionated course of radiotherapy. Site significantly influenced fractionation. Overall response rates of 82% were achieved. Fractionation did not appear to influence this. Ten patients received large field irradiation. Fifteen patients had five or more sites irradiated, of whom only one received hemibody irradiation.

Retreatment with radiotherapy for painful bone metastases.

PURPOSE: To evaluate the response to reirradiation of painful bone metastases following initial treatment with radiotherapy. METHODS AND MATERIALS: A retrospective analysis of 105 consecutive patients treated with palliative radiotherapy for painful bone metastases. A total of 280 individual treatment sites were identified, of which 57 were retreated once and 8 were retreated twice. RESULTS: The overall response rate to initial treatment was 84% for pain relief, and at first retreatment this was 87%. Seven of eight patients retreated a second time also achieved pain relief. No relation to radiation dose, primary tumor type, or site was seen. CONCLUSIONS: In patients relapsing after radiotherapy to painful bone metastases who have responded initially, reirradiation can be recommended with a similar probability of response.

Reduced bone mineral density in long-term survivors of medulloblastoma.

Bone mineral density (BMD) reaches a peak at approximately 30 years of age, and may be influenced by radiotherapy before completion of skeletal maturation. Regional BMD has been measured using dual energy X-Ray absorptiometry (DEXA) in adults following craniospinal irradiation for medulloblastoma between ages 4 and 19 years, receiving doses of 3500-4000 cGy to the brain and spinal cord. Lumbar spine (LS) and was failure to achieve normal adult BMD at both LS and FN, with a mean reduction at LS of 12.1% +/- 2.4% (p < 0.01) and a mean reduction at FN of 14.3% +/- 3.4% (p < 0.01). The mean body mass index (BMI) was also less than that of a standard population (21.8 +/- 1.5), as were mean standing and sitting heights. No relationship was found between reduction in BMD at either site and age at irradiation, time elapsed since irradiation or BMI at time of scanning. Biochemical and endocrine markers including corrected calcium, alkaline phosphatase, sex hormones and IGF-1 were normal in all seven patients. The reduction in BMD outside the irradiated area suggests that indirect factors may be important in this effect.

External beam radiotherapy for carcinoma of the prostate: a retrospective study.

Two hundred and thirty-seven consecutive patients receiving radiotherapy for primary prostatic carcinoma have been reviewed. The presenting symptoms included acute retention (29%), chronic outflow obstruction (78%) and haematuria (12%). The diagnosis was confirmed at trans-urethral resection of the prostate (TURP) in 95%; all but seven patients had adenocarcinoma. The clinical stage at presentation was T0 (3%), T1 (9%), T2 (49%), T3 (21%) and T4 (17%). Two hundred and six patients (87%) received primary radiotherapy, 38 (16%) had concurrent endocrine therapy. Local relapse alone occurred in 38 patients (16%), distant relapse alone occurred in 30 (13%), and both local and distant relapse occurred in 30 (13%). Median time to local relapse alone was 25 months, distant relapse alone 14 months, and local and distant relapse 22 months. Overall survival was related to stage and grade at presentation. No influence of endocrine therapy, dose or planning technique was seen, but a significant advantage for those patients treated using a planned volume compared with parallel opposed fields was observed. Acute radiation toxicity affecting the bladder occurred in 42% and the bowel in 45%. Late toxicity affecting the bladder occurred in 7% and the bowel in 2%.